Vitamin D functions as a powerful immune modulator, deficiency of vitamin D is highly prevalent among SLE patients, and preclinical studies have shown success using vitamin D to treat animal models of autoimmune disease. We have preliminary data demonstrating that Caucasian SLE patients have significantly lower vitamin D levels compared to controls, and there is a strong trend towards higher disease activity in patients with lower levels of 25-hydroxyvitamin D (25(OH)D). Evidence from prospective studies of RA and type 1 diabetes in humans suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. The overall hypothesis of this proposal is that vitamin D deficiency is a reversible environmental trigger of SLE and increased disease activity, and that supplementation with doses of vitamin D sufficient to achieve immune modulatory effects will be safe and attenuate disease activity in SLE patients. The Research Development Plan consists of 3 Aims. In Specific Aim 1, 25(OH)D and iPTH will be performed on stored serum samples from participants from 3 longitudinal cohorts to determine whether vitamin D deficiency correlates with SLE compared to controls, and with disease activity and severity among cases. In Specific Aim 2, we will determine the factors that protect the minority of African American SLE patients from becoming vitamin D deficient, assessing diet, sun exposure, supplement use, and skin pigment. Specific Aim 3 involves administration of oral vitamin D to deficient African American SLE patients in a small Phase I clinical study to establish safety, tolerability, and an effective dose for replacement therapy. Disease activity, disease flare, immunologic measures, inflammatory markers, and quality of life will also be assessed. The information gathered from this study will be used to plan a scientifically sound larger scale Phase ll/lll placebo-controlled trial. The Career Development Plan will consist of 5 essential components: (1) Research projects preceptorship overseen by a research advisory and mentorship committee; (2) Meetings and conferences; (3) Training in the responsible conduct of research; (4) Formal mentorship training; and (5) Formal coursework to further develop a body of knowledge in relevant areas. These research and career development aims are designed to provide training in techniques for the cross-sectional analysis of large databases and for the design and implementation of clinical research studies in an outpatient setting. The pursuit of these projects, in conjunction with formal coursework in biostatistical and epidemiological methods, is intended to foster Dr. Kamen's career as an independent academic clinical investigator with a focus on SLE and patient-oriented research. [unreadable] [unreadable] [unreadable] [unreadable]